Mastoiditis is the inflammation of a portion of the temporal bone referred to as the mastoid air cells. The mastoid air cells are epithelium lined bone septations that are continuous with the middle ear cavity.

The temporal bone is composed of four parts: the mastoid process, the petrous pyramid, the squamous, and tympanic portions. The mastoid process and the petrous pyramid are the portions of particular interest because of the prevalence of suppurations within these parts of the temporal bone.

Cytokines are a family of chemical messengers, secreted by leucocytes, that act over short distances by binding specific receptors on target cell surfaces. They include: interleukins (act between leucocytes), interferons (inhibit replication of viruses within cells and activate macrophages and natural killer cells), growth factors, and tumour necrosis factors (kill tumour cells). Effects include: induction of fever and acute phase response, stimulation of leucocyte differentiation and maturation, leucocyte recruitment and activation and increased antibody production.

Hepatitis B vaccines are prepared from the viral surface antigen. The recombinant vaccine is now the most widely used vaccine and induces a sufficient antibody response in 90% of individuals.
Indications for hepatitis B vaccination include:
All health care professional’s
Other professions with occupational risks (foster carers, staff of custodial institutions, morticians etc)
Babies of mothers with hepatitis B during pregnancy
Close family contacts of a case or carrier
IV drug abusers
Individuals with haemophilia
Individuals with chronic renal failure
Sex workers and individuals with frequently changing sexual partners
The vaccine should be stored between 2 and 8 degrees C as freezing destroys its efficacy. The vaccine is administered intramuscularly, either into the deltoid region (preferred) or anterolateral thigh. The buttock should be avoided as it reduces the efficacy of the vaccine.
The standard regime is to give 3 doses of the vaccine, the 1stand 2ndone month apart and the 2ndand 3rdsix months apart. Antibody titres should be tested 2 to 4 months after the primary course.
A peak titre above 100 mIU/ml is regarded as a good response and implies long-term immunity. A peak titre between 10-100 mIU/ml is regarded as a low response and a peak titre of less than 10mIU/ml is regarded as a poor response.
There is no substantiated association between hepatitis B vaccination and Guillain-Barre syndrome.

The arrangement of micelles is such that hydrophobic lipid molecules lie in the centre, surrounded by hydrophilic bile acids that are arranged in the outer region. This arrangement allows the entry of micelles into the aqueous layers surrounding the microvilli. As a result, the products of fat digestion (fatty acids and monoglycerides), cholesterol and fat-soluble vitamins (such as vitamin D) can then diffuse passively into the enterocytes. The bile salts are left within the lumen of the gut where they are reabsorbed from the ileum or excreted in faeces.

A cricothyrotomy involves making an opening in the median cricothyroid ligament (the medial part of the cricothyroid membrane), between the cricoid cartilage below and the thyroid cartilage above.

Lactic acidosis is a common finding in critically ill patients and commonly associated with other serious underlying pathologies. It occurs when pH is <7.35 and lactate is >5 mmol/L. Anion gap is increased in lactic acidosis.

Acquired lactic acidosis is classified into two subtypes:
Type A: lactic acidosis due to tissue hypoxia and
Type B: due to non-hypoxic processes affecting the production and elimination of lactate

Some causes of type A and type B lactic acidosis include:
Type A lactic acidosis
Left ventricular failure
Severe anaemia
Shock (including septic shock)
Asphyxia
Cardiac arrest
CO poisoning
Respiratory failure
Severe asthma and COPD

Type B lactic acidosis:
Regional hypoperfusion
Renal failure
Liver failure
Sepsis (non-hypoxic sepsis)
Thiamine deficiency
Alcoholic ketoacidosis
Diabetic ketoacidosis
Cyanide poisoning
Methanol poisoning
Biguanide poisoning

Gaussian distribution, also known as normal distribution, is the most important probability distribution in statistics because it fits many natural phenomena. The normal distribution is a probability function that describes how the values of a variable are distributed. Below are its characteristics:

(1) Bell-shaped and symmetrical about the mean
(2) The mean, median, mode are all equal
(3) The total area under the curve and above the x-axis is equal to 1
(4) It has long tapering tails extending infinitely but never touching the x-axis
(5) It is determined by its parameters: its mean and standard deviation
(6) The standard deviation becomes a more meaningful quality than merely being a measure of dispersion

The mean is the most common measure of central tendency. It is the sum of all observed values divided by the number of observation, and is also known as the ‘average’.

The median is the value that falls in the middle position when the observations are ranked in order from the smallest to the largest. If the number of observations is odd, the median is the middle number. If it is even, the median is the average of the two middle numbers.

The mode is the value that occurs with the greatest frequency in a set of observations, and is commonly used in public health statistics, such as the top 10 causes of mortality.

Abciximab (ReoPro) is a glycoprotein IIb/IIIa receptor antagonist that is a chimeric monoclonal antibody. It is primarily used during and after coronary artery procedures such as angioplasty to inhibit platelet aggregation.

It’s approved for use as a supplement to heparin and aspirin in high-risk patients undergoing percutaneous transluminal coronary intervention to prevent ischaemic complications. Only one dose of abciximab should be given (to avoid additional risk of thrombocytopenia).

Before using, it is recommended that baseline prothrombin time, activated clotting time, activated partial thromboplastin time, platelet count, haemoglobin, and haematocrit be measured. 12 and 24 hours after starting treatment, haemoglobin and haematocrit should be measured again, as should platelet count 2-4 hours and 24 hours after starting treatment.
When used for high-risk patients undergoing angioplasty, the EPIC trial(link is external)found that abciximab reduced the risk of death, myocardial infarction, repeat angioplasty, bypass surgery, and balloon pump insertion.

The use of abciximab is contraindicated in the following situations:
Internal bleeding is present.
Within the last two months, you’ve had major surgery, intracranial surgery, or trauma.
Stroke in the previous two years
Intracranial tumour
Aneurysm or arteriovenous malformation
Haemorrhagic diathesis is a type of haemorrhagic diathesis.
Vasculitis
Retinopathy caused by hypertension

The following are some of the most common abciximab side effects:
Manifestations of bleeding
Bradycardia
Back ache
Pain in the chest
Vomiting and nausea
Pain at the puncture site
Thrombocytopenia

Compression of the thecal sac causes metastatic Spinal Cord Compression (MSCC) due to a Metastatic tumour and its components. It can cause symptoms of limb weakness, sensory disturbances and back pain depending on the extent and level of Compression.

The most common source of a tumour causing MSCC is a prostate carcinoma that metastasized to the spinal cord via the vertebral venous plexus.

Elevation of the mandible is generated by the temporalis, masseter and medial pterygoid muscles.

Both the medial and lateral pterygoids are innervated by the mandibular division of the trigeminal nerve.

Raised platelet levels have emerged as a cancer risk marker, according to a large population-based study published in 2017(link is external). According to the study, 12 percent of men and 6% of women with thrombocytosis were diagnosed with cancer within a year. These figures increased to 18% in men and 10% in women if a second platelet count was taken within 6 months of the first and showed an increased or stable elevated platelet count.

The researchers discovered that thrombocytosis linked to cancer is most common in colorectal and lung cancers, and it is linked to a worse prognosis. Furthermore, one-third of the cancer patients in the study had no other symptoms that would have prompted an immediate cancer referral.

The exact mechanism by which these cancers cause thrombocytosis is unknown, but one theory proposes the existence of pathogenic feedback loops between malignant cells and platelets, with a reciprocal interaction between tumour growth and metastasis, as well as thrombocytosis and platelet activation. Another hypothesis is that thrombocytosis occurs independently of cancer but aids in its spread and progression.

The findings show that routinely testing for thrombocytosis could cut the time it takes to diagnose colorectal and lung cancer by at least two months. In the UK, this could result in around 5500 earlier cancer diagnoses per year.

Because the positive predictive value of thrombocytosis in middle age for cancer (10%) is higher than the positive predictive value for a woman in her 50s presenting with a new breast lump (8.5%), this is clearly an important research paper that should be used to adjust future clinical practise. The current NICE guidelines predate these new research findings, so we’ll have to wait and see how they affect cancer referral guidelines in the UK.

Because there are so many possible cancers associated with thrombocytosis, the treating clinician should take a thorough history and perform a thorough clinical examination if a patient is diagnosed with it. Further investigation and the most appropriate referral route should be aided by this information.

It’s worth noting that the patients in the study had their blood tests done for a medical reason rather than as a random screening test.

If there are no other symptoms to guide investigation and referral (one-third of the patients in the study had no other symptoms), keep in mind that the two most common cancers encountered were colorectal and lung cancer, so a chest X-ray and a faecal immunochemical test (FIT) for faecal blood may be reasonable initial investigations.

Bumetanide is a loop diuretic that inhibits sodium, chloride, and potassium reabsorption by acting on the Na.K.2Cl co-transporter in the ascending loop of Henlé. This reduces the osmotic gradient that forces water out of the collecting duct system and prevents the formation of a hypertonic renal medulla. This has a strong diuretic effect on the body.

It’s primarily used in patients with heart failure who aren’t responding to high doses of furosemide. Bumetanide and furosemide differ primarily in terms of bioavailability and pharmacodynamic potency.

In the intestine, furosemide is only partially absorbed, with a bioavailability of 40-50 percent. Bumetanide, on the other hand, is almost completely absorbed in the intestine and has a bioavailability of about 80%. Bumetanide is 40 times more potent than furosemide, and one milligram is roughly equivalent to 40 milligrams of furosemide.

Bumetanide also lowers the concentration of neuronal chloride, making GABA’s action more depolarizing. In the neonatal period, it is being studied as an antiepileptic.

The electron transfer system is responsible for most of the energy produced during respiration. The is a system of hydrogen carriers located in the inner mitochondrial membrane. Hydrogen is transferred to the electron transfer system via the NADH2 molecules produced during glycolysis and the Krebs cycle. As a result, a H+ion gradient is generated across the inner membrane which drives ATP synthase. The final hydrogen acceptor is oxygen and the H+ions and O2 combine to form water.

Innate immunity, also called non-specific immunity, refers to the components of the immune system naturally present in the body at birth.

The components of innate immunity include:
1) Natural Killer Cells
2) Neutrophils
3) Macrophages
4) Mast Cells
5) Dendritic Cells
6) Basophils.

Acquired or adaptive immunity is acquired in response to infection or vaccination. Although the response takes longer to develop, it is also a more long-lasting form of immunity.

The components of this system include:
1) T lymphocytes
2) B lymphocytes
3) Antibodies

Forest plots are graphical displays designed to illustrate the relative strength of treatment effects in multiple individual studies addressing the same question.

Majority of carbohydrates are broken down into monosaccharides (glucose, fructose galactose) and are absorbed by the small intestine. Enzymes released from the brush border break down carbohydrate. Some carbohydrates, such as cellulose, are not digested at all, despite being made of multiple glucose units. This is because the cellulose is made out of beta-glucose that makes the inter-monosaccharide bindings different from the ones present in starch, which consists of alpha-glucose. Humans lack the enzyme for splitting the beta-glucose-bond.

The principal brush border enzymes are dextranase and glucoamylase. Other brush border enzymes are maltase, sucrase, and lactase.

Pancreatic amylase breaks down some carbohydrates (notably starch) into oligosaccharides. Dextranase and glucoamylase, then further break down oligosaccharides.

Trypsin aids in digestion of protein.

Chymotrypsin is a proteolytic enzyme that digests protein

Carboxypeptidase hydrolyses the first peptide or amide bond at the carboxyl or C-terminal end of proteins and peptides

Malaria is an infectious disease transmitted by female of theAnophelesgenus of mosquito. It is a parasitic infection caused by the genusPlasmodium. Five species are recognized as causing disease in humans;Plasmodium falciparum,Plasmodium ovale,Plasmodium vivax,Plasmodium malariaeandPlasmodium knowlesi.
The classic symptom of malaria is the malarial paroxysm, a cyclical occurrence of a cold phase, where the patient experiences intense chills, a hot stage, where the patient feels extremely hot and finally a sweating stage, where the fever declines and the patient sweats profusely. On examination the patient may show signs of anaemia, jaundice and have hepatosplenomegaly without evidence of lymphadenopathy.

Plasmodium falciparum is the most serious form and is responsible for most deaths. Severe or complicated malaria is suggested by the presence of impaired consciousness, seizures, hypoglycaemia, anaemia, renal impairment, respiratory distress and spontaneous bleeding.
Plasmodium falciparum is the most likely type in this case in view of the presentation.
Haemoglobinuria and renal failure following treatment is suggestive of blackwater fever, which is caused byPlasmodium falciparum. An autoimmune reaction between the parasite and quinine causes haemolysis, haemoglobinuria, jaundice and renal failure. This can be fatal.
The benign malarias: P.vivax, P. malariae and P.ovale are usually treated with chloroquine. A course of primaquine is also required in P.vivax and P.ovale infection. Artesunate is the drug treatment of choice for Plasmodium falciparum malaria. Quinine can still be used where artesunate is not available. Often combination therapy with drugs such as doxycycline or fansidar is also required.

Eosinophils comprise 1 – 3% of circulating white cells. Eosinophils are similar to neutrophils, except that the cytoplasmic granules are coarser and more deeply red staining, and there are rarely more than three nuclear lobes. They are less motile, but longer lived. They enter inflammatory exudates and have a special role in allergic responses, defence against parasites and removal of fibrin formed during inflammation. Thus they play a role in local immunity and tissue repair.

Non-Hodgkin’s lymphoma (NHL) refers to a group of lymphoproliferative malignancies (about 85% of B-cell and 15% of T or NK (natural killer) cell origin) with different behavioural patterns and treatment responses. This group of malignancies encompasses all types of lymphoma without Reed-Sternberg cells being present. The Reed-Sternberg cell is classically seen in Hodgkin’s lymphoma.
NHL is five times as common as Hodgkin’s lymphoma. The peak incidence of NHL is in the 50-70 years age group, it affects men and women equally, but affects the Caucasian population more commonly than black and Asian ethnic groups.
The following are recognised risk factors for NHL:
Chromosomal translocations and molecular rearrangements
Epstein-Barr virus infection
Human T-cell leukaemia virus type-1 (HTLV-1)
Hepatitis C
Congenital and acquired immunodeficiency states
Autoimmune disorders, e.g. Sjogren’s syndrome and Hashimoto’s thyroiditis
The most common clinical features at presentation are:
Lymphadenopathy (typically asymmetrical and painless)
Weight loss
Fatigue
Night sweats
Hepatosplenomegaly
For clinical purposes, NHL is divided into three groups: indolent, high-grade, and lymphoblastic.
Indolent (low-grade) NHL:
The cells are relatively mature
Disease follows an indolent course without treatment
Often acceptable to follow a ‘watch and wait’ strategy
Local radiotherapy often effective
Relatively good prognosis with median survival of 10 years
High-grade NHL:
Cells are immature
Disease progresses rapidly without treatment
Significant number of patients can be cured with intensive combination chemotherapy regimens
Approximately 40% cure rate
Lymphoblastic NHL:
Cells are very immature and have a propensity to involve the CNS
Treatment and progression are similar to that of acute lymphoblastic leukaemia (ALL)

HIV mainly infects CD4+ T helper cells. Viral replication results in progressive T-cell depletion and impaired cell-mediated immunity with subsequent secondary opportunistic infections and increased risk of malignancy. B-cell function is also reduced as a result of lack of T-cell stimulation.
HIV is not a notifiable disease.

Brachioradialis is a fusiform muscle located in the lateral part of the posterior forearm. Along with extensor carpi radialis brevis and extensor carpi radialis longus, it comprises the radial group of forearm muscles, which belong to the superficial layer of posterior forearm muscles. Although anatomically part of the posterior forearm muscles, which are known to be forearm extensors, brachioradialis’ fibre orientation enables it to rather flex the forearm, and aids in supination of the forearm at the radioulnar joint.

The brachioradialis muscle originates from the upper two-thirds of the lateral supracondylar ridge of humerus and the anterior surface of the lateral intermuscular septum of the arm. It slides over the lateral surface of the elbow joint, entering the anterolateral cubital area. The muscle fibres course inferiorly down the radial part of the anterior forearm, forming a thick tendon in approximately the middle of the forearm. This tendon then traverses the remainder of the forearm, inserting near the wrist, just proximal to the styloid process of radius.

Brachioradialis is innervated by the radial nerve (from the root values C5-C6) that stems from the posterior cord of the brachial plexus. Blood supply to the brachioradialis muscle comes from branches of the radial artery, radial recurrent artery and the radial collateral branch of the deep brachial artery.

Gas exchange between alveolar air and blood in the pulmonary capillaries takes place by diffusion across the alveolar-capillary membrane. Diffusion occurs from an area of high partial pressure to an area of low partial pressure, thus the driving force for diffusion is the alveolar-capillary partial pressure gradient. Diffusion occurs until equilibrium is reached, but random movement of particles continues to occur and this is known as dynamic equilibrium. The diffusing capacity for oxygen (DLO2) cannot be measured directly but the rate of diffusion in the lungs can be estimated by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO), not by measuring total lung capacity. The rate of transfer of a gas may be diffusion or perfusion limited; carbon monoxide transfer is diffusion-limited, oxygen transfer is usually perfusion-limited.

Pectoralis minor is a thin, triangular muscle that is situated in the upper chest. It is thinner and smaller than pectoralis major. It is innervated by the medial pectoral nerve.
The origin of pectoralis minor is the 3rdto the 5thribs, near the costal cartilages. It inserts into the medial border and superior surface of the coracoid process of the scapula.
The main action of pectoralis minor is to draw the scapula inferiorly and anteriorly against the thoracic wall. This serves to stabilise the scapula.

Vaccination induces ACTIVE adaptive immunity. Actively acquired immunity involves the development of an immune response either due to vaccination or natural exposure to a pathogen and leads to long-lasting resistance to infection.

Immediate protection is achieved with injection of immunoglobulin. The protection is transient lasting only a few weeks and is useful as post-exposure prophylaxis.

Passively acquired immunity usually leads to short-lasting resistance to infection because it does not involve a host immune response.

With inactivated bacteria, a series of primary vaccinations is usually required to induce an adequate immune response. In most cases, boosters are required to sustain adequate immunity.

Pioglitazone is used to treat type 2 diabetes mellitus. It selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-γ) and to a lesser extent PPAR-α.

Of the medications mentioned in this question, only pioglitazone is a recognized cause of hypoglycaemia.

Dietary fat is chiefly composed of triglycerides. In the duodenum fat is emulsified by bile acids, a process where larger lipid droplets are broken down into much smaller droplets providing a greater surface area for enzymatic digestion. Once inside the epithelial cell, lipid is taken into the smooth endoplasmic reticulum where much of it is re esterified. Dietary and synthesised lipids are then incorporated into chylomicrons in the Golgi body, which are exocytosed from the basolateral membrane to enter lacteals. Chylomicrons consist mainly of triglyceride with small amounts of cholesterol and cholesteryl esters in the centre with a phospholipid coat studded with apolipoproteins. Fat-soluble are absorbed into enterocytes from micelles by simple diffusion together with the products of fat digestion.

E. coli may cause several different gastrointestinal syndromes. Based on virulence factors, clinical manifestation, epidemiology, and different O and H serotypes, there are five major categories of diarrheagenic E. coli, enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC), enteropathogenic E. coli (EPEC), enterohemorrhagic E. coli (EHEC), and enteroadherent, which includes diffusely adherent E. coli (DAEC) and enteroaggregative E. coli (EAEC). These five categories are sometimes
collectively referred to as enterovirulent E. coli or diarrheagenic E. coli.

Norwalk virus is part of the Caliciviridae family of viruses which are single-stranded RNA viruses and are the most common cause of infectious gastroenteritis in the US.

Rotaviruses are the most common cause of viral gastroenteritis
in infants and children. With the introduction in 2006 of a human-bovine rotavirus vaccine (RV5; RotaTeq, Merck), a delay in the onset of rotavirus
season was seen. RotaTeq is a series of three oral vaccines beginning at 6 to 12 weeks of age. A second vaccine, Rotarix (RV1; GlaxoSmithKline, Middlesex, England), was approved in June 2008.

Cryptosporidium causes an illness characterized by abdominal cramping, watery diarrhoea, vomiting, fever, and anorexia. This organism is resistant to chlorine, so public swimming pools can be the source of an outbreak.

G. lamblia has a worldwide distribution and has frequently been identified as the causative agent of outbreaks of gastroenteritis and traveller’s diarrhoea.

Adverse effects include:
Antimuscarinic effects: Dry mouth, Blurred vision, Constipation, Urinary retention, Sedation, Confusion
Cardiovascular effects: Heart block, Arrhythmias, Tachycardia, Postural hypotension, QT-interval prolongation, Hepatic impairment, Narrow-angle glaucoma

Hyperkalaemia causes a rapid reduction in resting membrane potential leading to increased cardiac depolarisation and muscle excitability. This in turn results in ECG changes which can rapidly progress to ventricular fibrillation or asystole. Very distinctive ECG changes that progressively change as the K+level increases:
K+>5.5 mmol/l – peaked T waves (usually earliest sign of hyperkalaemia), repolarisation abnormalities
K+>6.5 mmol/l – P waves widen and flatten, PR segment lengthens, P waves eventually disappear
K+>7.0 mmol/l – Prolonged QRS interval and bizarre QRS morphology, conduction blocks (bundle branch blocks, fascicular blocks), sinus bradycardia or slow AF, development of a sine wave appearance (a pre-terminal rhythm)
K+>9.0 mmol/l – Cardiac arrest due to asystole, VF or PEA with a bizarre, wide complex rhythm.